PROJECT SUMMARY Old age and obesity are prevalent risk factors for morbidity and mortality. Weight loss (WL) ameliorates many clinical consequences of obesity; yet despite its benefits, recommendation of intentional WL in older adults remains controversial. Reluctance stems, at least in part, from loss of bone mass known to accompany overall WL and the potential for exacerbation of age-related risk of osteoporosis and fracture. Addition of resistance exercise training (RT) to WL is an effective means to attenuate, but not stop, WL-associated reductions in bone mineral density (BMD); however, conventional RT interventions present barriers to long term feasibility (i.e., expensive equipment, on-site participation, safety supervision by trained staff, and waning compliance). Alternately, treating the WL-associated decrease in mechanical stress by replacing lost weight externally may also preserve bone mass. Pilot data from our institution signal that weighted vest use (designed to mimic weight stability) during WL is both feasible and likely efficacious in reducing WL-associated hip BMD loss while increasing biomarkers of bone formation. If confirmed, the greater availability, ease of administration, and reduced cost of weighted vest use to offset WL-associated bone loss, as compared to RT, holds significant public health potential as a translatable strategy to maximize the cardiometabolic benefits of WL, while minimizing negative implications for the musculoskeletal system. The main goal of the proposed R01 study is to compare the effects of WL alone and with weighted vest use or RT on several indicators of bone health and subsequent fracture risk. We propose a 12 month trial in 192 older (65-79 years) adults with obesity (BMI=30- 40 kg/m2) randomized to one of three interventions (n=64/group): WL alone (WL; caloric restriction targeting 10% WL and following national obesity treatment guidelines); WL plus weighted vest use (WL+VEST; ?6 hours/day, weight replacement titrated up to 10% WL); or, WL plus structured RT (WL+RT; 3 days/week, 10 exercises, 10-12 repetitions). Our primary study outcome is 12 month change in total hip trabecular volumetric BMD (vBMD) and we hypothesize that despite similar reductions in total body weight: (1) participants in the WL+VEST group will show attenuated losses of total hip trabecular vBMD versus WL, and (2) loss in total hip trabecular vBMD will be no greater in WL+VEST compared to WL+RT. Led by a talented New Investigator, this proposal is a natural extension of the work accomplished during the PI?s current MRSDA (K01 AG047291), and confers public health impact by testing a translatable strategy aimed at optimizing intentional WL in older adults with obesity while elucidating mechanisms governing musculoskeletal response to WL.